S-allyl cysteine alleviates nonsteroidal anti-inflammatory drug-induced gastric mucosal damages by increasing cyclooxygenase-2 inhibition, heme oxygenase-1 induction, and histone deacetylation inhibition

Background and Aim Nonsteroidal anti‐inflammatory drugs (NSAIDs), the most highly prescribed drugs in the world for the treatment of pain, inflammation, and fever, are associated with gastric mucosal damages including ulcer directly or indirectly. This study was aimed to document the preventive effects of an organosulfur constituent of garlic, S‐allyl cysteine (SAC), against NSAIDs‐induced gastric damages, as well the elucidation of its pharmacological actions, such as anti‐inflammatory, anti‐oxidative, and cytoprotective actions. Methods Different doses of SAC were administrated intragastrically before the indomethacin administration. After killing, in addition to gross and pathological evaluations of ulcer, the expressions of inflammatory mediators, including cyclooxygenase‐2, prostaglandin E2, IL‐1β, tumor necrosis factor‐α, IL‐6, and anti‐oxidant capacity, were analyzed by Western blot analysis or ELISA, respectively. Transferase deoxytidyl uridine end labeling assay, periodic acid and Schiff staining, F4/80 staining, and CD31 staining were compared among doses of SAC. Detailed documentation of in vitro biological actions of SAC, including NF‐κB, histone deacetylator inhibition, phase 2 enzyme, and MAPKs, was performed. Results SAC was very effective in preventing indomethacin‐induced gastric damages in a low dose through significant decreases in macrophage infiltration as well as restorative action. Indomethacin‐induced expressions of inflammatory mediators were all significantly attenuated with SAC in accordance with histone deacetylator inhibition. In addition, SAC significantly increased the total anti‐oxidant concentration and mucus secretion, and allows for a significant induction of HO‐1. However, these preventive effects of SAC were dependent on dosage of SAC; higher dose above 10 μM paradoxically aggravated NSAID‐induced inflammation. Conclusion Synthetic SAC can be promising therapeutics agent to provide potent anti‐inflammatory, anti‐oxidative, and mucosa protective effects against NSAID‐induced damages.